Adiposity‐Independent Effects of Aging on Insulin Sensitivity and Clearance in Mice and Humans

Objective Aging is associated with impaired insulin sensitivity and increased prevalence of type 2 diabetes. However, it remains unclear whether aging‐associated insulin resistance is due to increased adiposity or other age‐related factors. To address this question, the impact of aging on insulin se...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Obesity (Silver Spring, Md.) Jg. 27; H. 3; S. 434 - 443
Hauptverfasser: Ehrhardt, Nicole, Cui, Jinrui, Dagdeviren, Sezin, Saengnipanthkul, Suchaorn, Goodridge, Helen S., Kim, Jason K., Lantier, Louise, Guo, Xiuqing, Chen, Yii‐Der I., Raffel, Leslie J., Buchanan, Thomas A., Hsueh, Willa A., Rotter, Jerome I., Goodarzi, Mark O., Péterfy, Miklós
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States Blackwell Publishing Ltd 01.03.2019
Schlagworte:
Adiposity - physiology
Adult
Age
Aging
Animals
Body composition
Cardiovascular disease
Diabetes
Diet
Female
Glucose
Hispanic Americans
Homeostasis
Human subjects
Humans
Insulin resistance
Insulin Resistance - genetics
Laboratories
Male
Metabolism
Mice
Peptides
Phenotype
Physiology
Population
Studies
Weight control
ISSN:1930-7381, 1930-739X, 1930-739X
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Objective Aging is associated with impaired insulin sensitivity and increased prevalence of type 2 diabetes. However, it remains unclear whether aging‐associated insulin resistance is due to increased adiposity or other age‐related factors. To address this question, the impact of aging on insulin sensitivity was investigated independently of changes in body composition. Methods Cohorts of mice aged 4 to 8 months (“young”) and 18 to 27 months (“aged”) exhibiting similar body composition were characterized for glucose metabolism on chow and high‐fat diets. Insulin sensitivity was assessed by hyperinsulinemic‐euglycemic clamp analyses. The relationship between aging and insulin resistance in humans was investigated in 1,250 nondiabetic Mexican Americans who underwent hyperinsulinemic‐euglycemic clamps. Results In mice with similar body composition, age had no detrimental effect on plasma glucose and insulin levels. While aging did not diminish glucose tolerance, hyperinsulinemic‐euglycemic clamps demonstrated impaired insulin sensitivity and reduced insulin clearance in aged mice on chow and high‐fat diets. Consistent with results in the mouse, age remained an independent determinant of insulin resistance after adjustment for body composition in Mexican American males. Conclusions This study demonstrates that in addition to altered body composition, adiposity‐independent mechanisms also contribute to aging‐associated insulin resistance in mice and humans.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
Author contributions: N.E. conducted experiments, analyzed data and revised the manuscript. J.C. analyzed data. S.D. and S.S. conducted experiments. H.S.G. provided materials and advised experiments. J.K.K. and L.L. supervised experiments, analyzed data and revised the manuscript. X.G., Y.I.C., L.J.R., T.A.B., W.A.H. and J.I.R acquired data. M.O.G. and M.P. conceived of the study design, supervised the study, analyzed data, and revised the manuscript. M.P. wrote the manuscript. All authors approved the final version of the manuscript.
ISSN:1930-7381
1930-739X
1930-739X
DOI:10.1002/oby.22418